Porphyrins are natural substances and structural precursors of heme. These tetrapyrroles have chemical properties that make them particularly useful in the diagnosis and treatment of cancer. Porphyrins are potent photosenitizers and absorb radiant energy in the Soret band (400-410 nm) and in the red portion of the visible spectrum (600-650 nm). Many neoplasms in experimental animals and in the human population are known to have a selective affinity for porphyrins. Few studies have been conducted to determine the feasibility of using the photo-sensitizing properties of porphyrin for the diagnosis and treatment of cutaneous neoplasms. The studies proposed here will systematically evaluate the photosensitizing properties of hematoporphyrin derivative (HPD) in human skin cells (normal and malignant) and in an experimental animal model of UV-induced squamous cell carcinoma (the hairless mouse). The uptake and distribution of HPD, dose-response relationships (light and HPD) and action spectra will be determined in the cultured cells and in the animal model. Furthermore, these studies are designed to develop new knowledge concerning the toxic mechanism of porphyrin photosensitization for skin cells and cutaneous tumors. Once definitive data have been accumlated in the experimental systems, it is planned to study a small number of human subjects with non-melanoma skin cancer (primary and recurrent) as well as patients with the basal cell nevus syndrome. Efforts will be made to localize HPD in these lesions and to determine the usefulness of HPD in identifying early lesions, in defining the border between malignant and normal tissue, and in treating selected small neoplastic lesions. The major thrust of these studies is to determine whether porphyrin photosensitization is useful in the diagnosis and treatment of human skin cancer.